Serum amyloid A (SAA) is an acute phase reactant that was detected within the past decade by its cross-reaction with antibodies raised to denatured amyloid A Fibrils. The origin and structure of SAA and its role in the pathogenesis of secondary amyloidosis has been investigated, employing the mouse as an experimental model. Induction of the acute phase SAA response by inflammatory agents such as endotoxin has thus far been observed only in vivo. We have shown that two cell populations are involved in the acute phase SAA response to lipopolysaccharide (LPS). A macrophage response to LPS gives rise to SAA inducer, which in turn stimulates SAA synthesis by liver and possibly other tissues. Three stages in the SAA response to LPS and other agents of inflammation have been observed: a latent period of 2 to 3 hours during which the SAA concentration remains at baseline values and in which SAA inducer appears; the period of SAA synthesis which lasts for 24 hours past induction, and the period of deinduction during which SAA synthesis ceases and SAA concentration returns to baseline values by 48 hours after induction.